The incidence of small cell lung cancer (SCLC) accounts for about one-third of all lung cancers, and 10% to 15% of lung cancers, with high degree of malignancy. SCLC is featured by rapid progression and distant metastasis soon after diagnosis. Almost ⅔ of SCLC patients are at an advanced stage when diagnosed. So far, chemotherapy is still the main treatment method. Chemotherapy and radiotherapy work in patients at the initial stage; however, most patients still relapse within 2 years and die from systemic metastasis. In the past few decades, its treatment has not been significantly changed, resulting in patient's overall 5-year survival rate less than 7%. Based on a postgraduate's degree dissertation of China Medical University issued in May 2013, named as ‘A retrospective study of first-line treatment of extensive-stage small cell lung cancer using topotecan as compared with etoposide plus cisplatin’, it is pointed out that CAV (cyclophosphamide+doxorubicin+vincristine) treatment for small cell lung cancer has been developed into etoposide plus cisplatin chemotherapy regimen.
In recent years, researchers have tried to use multiple chemotherapy regimens and new cytotoxic drugs have been approved for treatment evaluation of relapsed SCLC, among which there are few clinically promising drugs. For patients relapsed with SCLC who are physically admissible, second-line chemotherapy and above should be given. Topotecan is the only second-line drug approved by the FDA for SCLC, however, its effectiveness is only the same as the CAV regimen. In the phase I clinical study, reported by Agelaki et al., ‘A phase I clinical trial of weekly oral topo-tecan for relapsed small cell lung cancer’, Cancer Chemotherapy and Pharmacology’, 2013 April, 72 (1), dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of topotecan were investigated in patients with relapsed SCLC who were orally given topotecan every week. 18 Patients were orally given topotecan on Day 1, 8 and 15, lasting 28 days as a course of treatment. The initial dose was 3 mg/m2, followed by an increasing dose of 0.5 mg/m2 until MTD. 13 Patients underwent second-line treatment, and 5 patients underwent third-line treatment or above. The results showed that DLT appeared at 4.5 mg/m2 and MTD was 4 mg/m2. DLT included II-III degree neutropenia and II degree thrombocytopenia. The most common toxic side effects were II-III degree neutropenia (27.8%), II-III degree anemia (33.3%), II degree thrombocytopenia (16.7%) and II-III degree fever (44.4%). The results showed that the effectiveness of topotecan was 11.1%, the median progression-free survival (PFS) was 2.3 months, and median survival (OS) was 5.1 months. The results of this study confirmed that as the only second-line drug for treating small cell lung cancer approved by FDA, topotecan exhibited effectiveness of about 10% and may cause serious side effects on blood and bone marrow.
The combined use of different types of drugs may overcome the problem of drug resistance. Currently, progresses on targeted treatment of SCLC has been made, but so far no ideal therapeutic drug has been obtained. Currently, among drugs for clinical treatment of relapsed SCLC, except topotecan and amrubicin, most of them were not evaluated by a randomized controlled study with a large sample size. Further, although drug combination therapy is effective for a small number of patients, especially for refractory and relapsed patients, it is not suitable for patients with poor clinical status. The effectiveness is poor in refractory and relapsed patients. Even according to the Jacot research results, which provided better results than others, among 70 patients from September 1992 to August 2010, 55 patients achieved objective remission, in the meanwhile only 10% of them appeared to maintain their disease situation. The median survival time was only 3.9 months. The occurrence of III-IV degree side effects was relatively high, with the blood system involved: neutropenia (71%), thrombocytopenia (23%) and anemia (22%).
Although some researches and developments of bio-targeted treatment drugs for SCLC have been conducted around the world, there has been no breakthrough progress in clinical trials and it is only theoretically suggested that there may be potential prospects in treatment of small cell lung cancer.
In summary, globally, there are no effective and efficient drugs for treating small cell lung cancer that can greatly prolong a patient's survival, much less healing. Therefore, in the field of cancer treatment and anti-tumor drug development it is urgent to develop effective and efficient drugs against small cell lung cancer that can improve the remission and survival rate of SCLC, in the field of cancer treatment and anti-tumor drug development.